The present invention generally relates to a radiation apparatus or installation for treatment of various types of cancer tumours, and the invention is more particularly directed to a neutron radiation apparatus/installation for treatment of cancer and of the type which emits neutron beams having a neutron energy of up to 40 keV, and in which the source of neutrons is preferably a nuclear reactor formed with a filter providing a radiation field having preferred low energy neutrons by means of which the tumour is irradiated.
The invention has, in the first place, been developed as the solution of the problem of irradiating tumours in the brain of humans and animals, which tumours have so far been considered extremely difficult to treat. It is, however, obvious that the invention is as well useful for treatment of many other types of tumours and types of cancer.
During the development of the invention there has, in the first place, been used a nuclear set up at Studsvik, Sweden, in the following referred to as R2-0. This is, of course, no limitation of the invention, but many other types of similar reactors can as well be used, like also accelerator based neutron sources, in which the neutrons are produced for example by the known reaction Li7 (p, n)xe2x86x92Be7, in which an accelerated beam of protons (p) is directed to a radiation target comprising the lithium isotope Li7, whereby neutrons (n) are emitted resulting in the beryllium isotope Be7 as the final product.
Shortly after the discovery of the neutron (1932) Locher suggested that neutron beams, in combination with isotopes having a high cross section (high probability) for absorption of neutrons, could be a method of radiation treatment of tumours. The nuclear process which has, in the first place, been discussed to this application is absorption of neutrons in the isotope boron-10
n+B10xe2x86x92B11*xe2x86x92Li7+He4+2.35 MeV.
A boron compound is introduced in the body, whereby the boron compound directs itself to cancer cells and is sucked into same and/or is positioned on the surface of the cancer cell. The reaction is that the B10 core absorbs/captures a neutron and is transformed to B11 which spontaneously is decomposed to the nuclear fragments Li7 and He4 having a combined kinetic energy of 2.35 MeV (million electron volt). The fragments are electrically charged and therefore strongly ionized along their paths in the surrounding material. The interaction with for instance biologic tissues is so effective that the fragments are completely braked to stop at a distance of 5-10 micrometer (millions of meter), which is the approximate dimension of a human cell. The energy in the molecular cell bond is of the magnitude of some few eV, and the fragments, having an energy of the magnitude of millions of electron volt breaks during its way through the cell millions of molecular bonds, and this is sufficient for destroying the reproductive ability of the cell. If the nuclear process is performed underneath the surface or in the core of a cancer cell the uncontrolled cell splitting is thereby stopped. If a sufficient number of cancer cells are accordingly inactivated the cancer is remedied.
The probability that a cancer cell is knocked out is a product of the probability that there is a B10 core on or in the cell and the probability that said B10 cord absorbs/captures a neutron is thereby transferred to B11 and thereby spontaneously becomes decomposed. The method is named BNCT method (Boron Neutron Capture Therapy). The effectiveness of said method is strongly restricted by the demand that the radiation is not allowed to introduce harmful dose concentrations on healthy tissues, what in turn puts demands both on the boron distribution in and on the tumour cells and the spreading of the neutron field and the energy distribution in the tumour and in healthy tissues.
The problem with deposition of boron or the boron compound in the cancer cell is a question raised in the biochemical research work, where extensive work is being made for providing effective target seeking substances. To-day there is a product on the market (named BPA) which is the amino acid phenylalanine which has been charged with boron atoms, which product issues an excess of boron in the tumour cells as compared with that of healthy tissues by a factor of about three. Other types of boron carrying substances can be used for the same purpose.
The second factor of importance for the therapeutic effect is the spreading of the neutron field in the tissue and the energy distribution of the neutrons in the tumour and in healthy tissues. Said questions belong to the neutron physical research field.
The energy distribution of the neutron beam is of decisive importance for the effect of the therapy in several respects. Firstly the probability that the neutrons are absorbed/captured in the B10 core, that is the desired therapeutic effect, is strongly depending on the energy. The probability is inverse proportional to the speed xe2x80x9cvxe2x80x9d of the neutron (so called 1/V cross section) and is therefore a high probability for slow (low energy) neutrons. This means that there is a wish for a radiation field having low energy neutrons at the tumour. A complication is that the dose load on healthy tissues is also depending on the neutron energy. The low energetic components in the radiation field both leads to capture in B10 in healthy tissues and also to capture in nitrogen and hydrogen cores in the tissues with a resulting non desired emission of reaction fragments and gamma radiation.
For deeply located tumours the situation is further more complicated in that a field of low energetic neutrons is quickly dampened during the passage thereof through the tissue, since this leads to a neutron intensity which is decreasing from the surface of the tissue with a relatively high dose load on the skin and intermediate healthy tissue. The principle method of improving the situation is to perform the radiation by means of neutrons which in the starting position has a relatively high energy. During the passage through the tissue the neutrons are braked by collision with atom nucleus in the tissue (in front of all hydrogen) so that a maximum of slow neutrons in thermal balance with the tissue (thermal neutrons) are built up 2-4 cm from the surface with a tail of low energy neutrons on further distances in the tissue.
Also this method is limited since too high neutron energies lead to a serious dose loads of other type. At a collision of a neutron with a hydrogen core a large part of neutron energy is transferred to the recoiling hydrogen core which, in turn, strongly ionizes (destroys) the tissue. The optimum compromise between said contradictory terms is to execute the radiation with neutrons in an intermediate area of the energy scale, namely by means of so called epithermic neutrons in the area between 1 eV and 40 keV, or preferably between 1 eV and about 20 keV. This can be done in that the neutrons which are produced in the reactor and which has energies in the MeV area are xe2x80x9cfiltered offxe2x80x9d by means of a filter block comprising elements having appropriate neutron physical properties. In the filter there is obtained a selective spreading and retardation of the neutrons, and from the output of the filter there is obtained a radiation beam by neutrons which are relatively evenly distributed in the energy area of 1 eV-40 keV, or preferably 1 eV-20 keV.
This method represents the known technology on which BNCT installations in USA (Brookhaven and MIT) and in Finland (Otaniemi) are based.
The neutron physical requirements for a BNCT installation are far better at the R2-0 reactor than in any existing installation all around the world depending on the specific construction of the Studsvik reactor, which is diagrammatically shown in FIG. 3 and which is to be described in the following. The reason is that the reactor core in the Studsvik reactor R2-0, differing from many other reactors, lacks both a permanent reflector and a reactor tank. The core hangs freely in the reactor pool and an optimum configuration of filter material can be installed in a filter between the reactor core and the radiation position for the patient.
The diagram of FIG. 1 shows the intensity and the energy distribution of the neutron beam at the patient position in the installation in Finland (FIR1), curve and in the suggested and so far planned installation at Studsvik R2-0, curve 2. From the diagram is evident that the intensity of epithermic neutrons is ≈10 times higher in the R2-0, curve 2, than in the Finnish installation, curve 1. As will be discussed in the following also the energy distribution and other radiation parameters are slightly more favourable in R2-0 than in other installations.
Other radiation properties of importance for the therapy outcome are the direction distribution of the neutronsxe2x80x94neutrons in a parallel beam of rays gives an optimum radiation field in the tissuexe2x80x94and the level of gamma radiation from the reactor and from neutron capture processes in the radiation filter. A group at INEEL, Idaho Falls, USA, has built up a library of computer programs (PPS=Patient Planning Software) by means of which the therapy effect of BNCT beams having given physical parameters can be calculated. In the program the outcome of the radiation is calculated in the form of the factor xe2x80x9cTumour Control Probabilityxe2x80x9d as a function of the dose load on healthy tissue, see FIG. 2. Considering the radiation parameters which have been discussed above it is also possible, by means of said program PPS, to generate the theoretically optimum radiation properties for treatment of tumours at different depths in the tissue, see xe2x80x9coptimum curve 2xe2x80x9d in FIG. 2. In the diagram the ideal beam for treatment of a brain tumour at the depth of 8 cm (most difficult case) is represented by the graph BNCTxe2x80x941, curve 3. Other graphs in the diagram refer to the results for the corresponding cases for the most important BNCT beams which are at present available in the west world. The beams are represented according to the following:
The outcome for the beam having a conventional filter which is planned to be used in the R2-0 reactor is represented by the graph marked by S544, curve. As evident from the diagram the beam at R2-0 can be expected to give a better treatment result than any of the other beams. This is obvious in that the curve shows that the radiation dose against healthy tissue is substantially less (curve is located further to the left) than from other installations, curves 4, 5 and 6.
During the last half-year an extraordinarily important further development of the neutron technology has been made for the R2-0 installation at Studsvik. The starting point for said development is the fact that the neutrons having low energies in the epithermic spectrum give, seen relatively, a worse contribution to therapy effect at a given dose load on healthy tissue.
By filtering off neutrons up to a certain energy, the value of which is determined by depth on which the actual tumour is located, the outcome of the radiation thereby can be improved. The technical problem in providing this is to find a filter material which selectively removes, by spreading processes in the filter material, neutrons having a relatively low energy, up to energies in the area of some few keV, without too much damping, concurrently therewith, the intensity of neutrons having relatively higher energies which are necessary for the radiation treatment, or which too much affects the direction distribution in the therapy beam. An optimum choice for this purpose is a plate of metallic lithium, or another form of the element lithium which is enriched up to =95% in the isotope Li6. In FIG. 4 is shown the neutron cross section for Li6. From the figure is evident that the absorption/capture is high for low energies and thereafter decreases quickly when the energy is increases, and this makes it possible to filter off neutrons having low energies. From the figure is also evident that the spreading cross section is low for energies in the interesting energy area of 1 eV-40 keV. The peak of the cross section curves at =250 keV is another advantage since it contributes to dampen the intensity of neutrons at high energies which have passed the conventional filter.
In the diagram of FIG. 1 is shown, by curve 8, the change of the energy distribution by an addition of a 2 cm thick Li filter mounted between the conventional standard filter of the reactor and the patient to be radiation treated. The graph having the designation S577, curve 9 of FIG. 2, shows that the R2-0 beam having said filter configuration is equivalent to the above mentioned ideal beam as hypothetically calculated. This is surprising and unique. For treatment of tumours at other depths than 8 cm the optimum result is obtained by varying the thickness of the Li filter.